Efficacy and Safety of Circumcision Alone on Risk of Febrile Urinary Tract Infections in Boys With Posterior Urethral Valves: a Prospective Randomized Open-label Multicentric Trial Enriched With Historic Controls.
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Antibiotics strategy, Circumcision.
- Who it may be relevant to
- Registry conditions: Posterior Urethral Valves. Basic parameters: 1 Day — 31 Days · Male.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
Boys with posterior urethral valves (PUV) are at increased risk of developing febrile urinary tract infections (fUTIs). As shown in the CIRCUP trial, circumcision plus antibiotic prophylaxis reduces the risk of FUTIs compared with antibiotic prophylaxis alone. This multicenter randomised controlled trial prospectively compares circumcision alone with circumcision plus antibiotic prophylaxis for the prevention of fUTIs in boys with PUV, enriched with external historical data from the CIRCUP trial)
Detailed description
Posterior urethral valves (PUV) are the most common cause of Lower Urinary Tract Obstruction (LUTO) in boys. They affect around 1:5000 births, causing increased intravesical pressure during fetal kidney development. They are associated with congenital renal dysplasia, abnormal bladder function and represent the most common obstructive cause of End-Stage Renal Failure in childhood. Postnatal primary valve ablation is the treatment of choice.
Despite optimal postnatal management, these patients present an increased risk of febrile urinary tract infection (fUTI). Febrile urinary tract infections in infants cause morbidity, require intravenous treatment and if they recur, can contribute to renal damage. Long-term prophylactic antibiotic treatment was therefore, until recently, the standard of care.
At the same time, circumcision was also supposed to decrease the rate of fUTI. This is why we conducted, between 2012 and 2017, the CIRCUP randomized controlled trial (PHRC-I) to determine whether circumcision in addition to antibiotic prophylaxis further decreased the risk of fUTI in boys with PUV, within the first two years of life.
We chose boys with PUV as they were undergoing surgery for their valve resection in any case, and the circumcision did not require an additional anaesthesia.
The results of the CIRCUP study were clear. The risk of fUTI was 3% in the Circumcision and antibiotic prophylaxis group vs 20% in the antibiotic prophylaxis alone group (RR: 10.3 (95% CI: 1.3 - 82.5)) (Circumcision and risk of febrile urinary tract infection in boys with posterior urethral valves. Harper L et al. 2022. Eur Urol (5), Annex 1).
The results from this study brought us, as well as several other teams (who either contacted us directly or as comments to our published study) to question the utility of antibiotic prophylaxis in circumcised boys with PUV (antibiotic prophylaxis has potential deleterious effects, both individually, and in terms of public health perspective). Circumcision alone could be a legitimate prophylactic strategy, in terms of balance between efficacy and risk of promoting antibiotic resistance.
We therefore aim to conduct a new clinical trial in boys with PUV to assess the effects of circumcision alone (without antibiotic prophylaxis) on the risk of fUTI using an efficient randomized trial design in this pediatric rare disease setting by incorporating data from the previous CIRCUP trial. This would allow us the identify risk of presenting a febrile UTI in circumcised boys with PUV and no antibiotic prophylaxis. This would help us determine the optimal strategy for UTI prevention in this population and discuss options with the parents.
Interventions
- Drug Antibiotics strategy
daily antibiotic prophylaxis up to two years - Procedure Circumcision
Circumcision performed at the time of valve resection
Primary outcome measures
- Time to first febrile urinary tract infections (fUTI) between baseline and 2 years [Time frame: between baseline and 2 years]
Secondary outcome measures (5)
- Median number of fUTIs [Time frame: at 2 years]
- The proportion of children with worsening renal scans (defined as an increase in heterogeneity and number of cortical defects) [Time frame: between baseline and 2-years]
- Absolute risk difference of first fUTI with circumcision alone versus circumcision and antibiotic prophylaxis [Time frame: at 2 years]
- Absolute risk difference of first fUTI with circumcision alone versus antibiotic prophylaxis alone [Time frame: at 2 years]
- Absolute risk difference of first fUTI with circumcision and antibiotic prophylaxis versus antibiotic prophylaxis alone [Time frame: at 2 years]
Eligibility criteria
\- Inclusion Criteria:
For prospective groups:
Male child aged 1 to 31 days Posterior urethral valves diagnosed by cystography within the first 28 days of life Valve resection and circumcision performed before 1 month of life. Adult guardians (>18 years) Parental guardians affiliated with a social security system Parental guardians who have signed an informed consent allowing their child to participate in the study Parental guardians giving consent must be able to understand the trial in its entirety
For retrospective groups from CIRCUP : Parental guardians who are not opposed to their child's participation in the trial
\- Exclusion Criteria: Mental state rendering the person giving consent incapable of understanding the trial Parents being a relative of the investigator or a relative of someone from the team directly involved in the trial, including assistant doctors, pharmacists, nurses, and trial coordinators Known contra-indication to all antibiotics used in the study (alfatil, Bactrim, augmentin) Long-term antibiotics use indicated for other reasons than PUV
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Prevention
Study locations
France · 13 centers
- CHU de Besançon — Besançon
- CHU de Bordeaux — Bordeaux
- CHU de Limoges — Limoges
- APHM — Marseille
- CHU de Montpellier — Montpellier
- CHU de Nantes — Nantes
- APHP Hôpital Armand Trousseau — Paris
- APHP Hôpital Necker — Paris
- … and 5 more centers
Publications
- Harper L, Blanc T, Peycelon M, Michel JL, Leclair MD, Garnier S, Flaum V, Arnaud AP, Merrot T, Dobremez E, Faure A, Fourcade L, Poli-Merol ML, Chaussy Y, Dunand O, Collin F, Huiart L, Ferdynus C, Sauvat F. Circumcision and Risk of Febrile Urinary Tract Infection in Boys with Posterior Urethral Valves: Result of the CIRCUP Randomized Trial. Eur Urol. 2022 Jan;81(1):64-72. doi: 10.1016/j.eururo.2021 PMID 34563412
Identifiers
NCT: NCT07527442 · CHUBX 2023/52 · 2024-519166-48-01